Pilot Study of Betaine + Combination Antiviral Therapy for Chronic Hepatitis C Genotype 1 Non-responder/Relapsers

NCT00882193 | Terminated Early Phase 1 DMC

• 1 other identifier: 0133-09-FB
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized, open-label study examining the safety and efficacy of betaine in addition to standard anti-viral therapy in genotype 1 hepatitis C non-responders or relapsers to previous pegylated interferon plus ribavirin. Betaine (20 gm/day) in 2 divided doses will be added to Peginterferon alpha 2a (180 mcg) plus weight-based Ribavirin (1000 or 1200 mg/day, for body weight \< or \> 75 kg, respectively, for 48 weeks. Patients must be diagnosed with chronic hepatitis C, genotype I, and have undergone therapy for hepatitis C with pegylated interferon plus ribavirin. Subjects will be followed for safety, tolerability, hepatitis C viral response and the effect on interferon gene signaling in peripheral blood mononuclear cells during therapy.

Conditions

Chronic Hepatitis C; Genotype 1; Relapse

Keywords

Chronic hepatitis C; Genotype 1; Nonresponder; Relapser; Betaine; Antiviral therapy

Outcome Measures

Primary Outcomes (1)

• Safety and efficacy of betaine combined with standard antiviral therapy

  To examine the safety and efficacy of betaine when combined with standard antiviral therapy in previously treated subjects with chronic hepatitis c genotype 1

  72 weeks

Secondary Outcomes (1)

• Effect on interferon gene signaling in peripheral blood mononuclear cells

  72 weeks

Study Arms (1)

Safety & Efficacy of Betaine Combined with Standard Anti-viral Therapy

EXPERIMENTAL

The primary objective is to examine safety \& efficacy of betaine when combined with standard anti-viral therapy in previously treated adult subjects with chronic hepatitis C infected with genotype 1. Efficacy will be determined through comparison of the sustained viral response (SVR) to our protocol three-drug regimen (Betaine, Peginterferon plus Ribavirin) to that historically seen in relapsers and non-responders when retreated with standard therapy (Peginterferon and Ribavirin alone). Betaine (trimethylglycine) dose is 10 gm twice a day for 48 weeks. Pegasys (peginterferon alpha 2a) dose is 180mcg/0.5 ml subcutaneous injection for 48 weeks. Coegus (ribavirin) dose is 200mg - weight based, 1000 - 1200 mg/day for body weight or 75mg in 2 divided doses.

Drug: Betaine; Drug: Peginterferon alpha 2a; Drug: Ribavirin

Interventions

Betaine DRUG

Betaine 20 gm/day in 2 divided doses for 48 weeks

Also known as: trimethylglycine

Safety & Efficacy of Betaine Combined with Standard Anti-viral Therapy

Peginterferon alpha 2a DRUG

Peginterferon alpha 2a 180mcg/0.5ml by subcutaneous injection weekly for 48 weeks

Also known as: Pegasys

Safety & Efficacy of Betaine Combined with Standard Anti-viral Therapy

Ribavirin DRUG

Ribavirin 200mg - weight based, 1000 - 1200 mg/day for body weight \< or \> 75mg in 2 divided doses

Also known as: Copegus

Safety & Efficacy of Betaine Combined with Standard Anti-viral Therapy

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be willing to give informed consent and be able to adhere to dose and visit schedules.
• History of chronic hepatitis C, genotype 1, non-responders or relapsers as documented by genotype testing and HCV RNA levels at 12 weeks ( \< 2 log change) during therapy or at 3 - 12 months post therapy, respectively.
• Adult subjects 18-70 years of age, of either gender
• Liver biopsy within 3 years prior to the screening 1 visit with a pathology report confirming that the histological diagnosis is consistent with chronic hepatitis C.
• Compensated liver disease with the following maximum hematologic, biochemical and serologic criteria at the Screening visit (WNL=within normal limits) Hemoglobin \> 12 g/dl for females and \>13 g/dl for males, WBC \> 3000/mm3, Platelets \> 80,000/mm3, Direct Bilirubin - WNL. Indirect bilirubin - WNL, Albumin - WNL, Serum Creatinine - WNL.
• Fasting glucose should be 70 -140 mg/dl, results between 116-140 require a HbA1c \< 8.5%
• TSH - WNL
• Subjects with a history of mild depression may be considered for entry in to this study provided that a pretreatment assessment of the subject's affective status supports that the subject is clinically stable.
• Subjects with a history of substance abuse must have abstained from using the substance for at least one year prior to the Screening visit.
• Antinuclear antibodies (ANA) \< 1:320
• No radiologic evidence of a focal mass suggestive of hepatoma and/or ascites.

You may not qualify if:

• Pregnant or nursing subjects. Subjects who intend to become pregnant during the study period. Subjects with partners who intend to become pregnant during the study period.
• Prior response to therapy and failure to achieve SVR which may have been due to treatment non-compliance, in the assessment of the investigator based upon subject's medical history.
• Participation in any clinical trial of a HCV protease inhibitor of any duration. Subjects may have received other investigational agents for the treatment of HCV, as long as they have also received an adequate course of Peg-IFN/RBV \[i.e., the investigational agent could not have replaced either Peg-IFN (such as Albuferon) or RBV (viramidine)\].
• History of new hepatitis C exposure within the last 6 months
• Current or intended use of G-CSF and/or GM-CSF during the stud period is prohibited. Current use of erythropoietin (EPO) is prohibited.
• Suspected hypersensitivity to any interferon product or ribavirin
• Participation in any other clinical trial within 30 days of Screening visit 1
• Treatment with any investigational drug within 30 days of Screening visit 1.
• Any other cause for liver disease other than CHC, including but not limited to: hemachromatosis, Alpha-1 antitrypsin deficiency, Wilson's disease, Autoimmune hepatitis, Alcoholic liver disease, Non-alcoholic steatohepatitis (NASH), Drug-related liver disease
• Known coagulopathies including hemophilia
• Known hemoglobinopathies
• Known G6PD deficiency
• Known coinfection with HIV and/or HBV
• Evidence of active or suspected malignancy or a history of malignancy within the last five years (with the exception of adequately treated basal cell carcinoma of the skin).
• Evidence of decompensated liver disease such as history or presence of ascites, bleeding varices or hepatic encephalopathy

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Recurrence

Interventions

Betaine; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Mark E Mailliard, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2009
• First Posted: April 16, 2009
• Study Start: May 1, 2009
• Primary Completion: January 12, 2011
• Study Completion: January 12, 2011
• Last Updated: November 30, 2023

Record last verified: 2023-11

Locations

US (1)